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Glycine Attenuates Citrobacter rodentium ‐Induced Colitis by Regulating ATF6‐Mediated Endoplasmic Reticulum Stress in Mice
Author(s) -
Zhang Yunchang,
Jiang Da,
Jin Yuhang,
Jia Hai,
Yang Ying,
Kim In Ho,
Dai Zhaolai,
Zhang Jinhua,
Ren Fazheng,
Wu Zhenlong
Publication year - 2021
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.202001065
Subject(s) - citrobacter rodentium , atf6 , unfolded protein response , colitis , biology , endoplasmic reticulum , immunology , microbiology and biotechnology , medicine , biochemistry
Scope Inflammatory bowel disease (IBD) is an inflammatory gastrointestinal disorder in which endoplasmic reticulum (ER) stress and dysbiosis of the intestinal microbiota are implicated. Glycine supplementation is reported to reduce inflammatory responses in experimental colitis. However, the underlying mechanisms responsible for the beneficial effects remain unclear. Methods and Results Female C57BL/6 mice are orally administered with glycine (3.5 or 5.2 g kg ‐1 body weight) for 14 continuous days. On day 8 post‐glycine supplementation, the mice are orally inoculated with 2 × 10 9 CFU Citrobacter rodentium ( C. rodentium ). The results show that glycine alleviates C. rodentium ‐induced body weight loss, increased disease activity index and spleen weight, colon length shortening, and colonic hyperplasia. Glycine suppresses the activation and infiltration of inflammatory cells, and secretion of pro‐inflammatory cytokines in the colon tissues. The apoptosis of colon epithelial cells is also abrogated by glycine, which is associated with the inactivation of activating transcription factor 6α (ATF6α)‐C/EBP homologous protein (CHOP) signaling. In addition, glycine administration increases α diversity, restores β diversity, and abolishes the reduction in Lactobacillus , Bifidobacterium , Alistipes , Turicibacter , and Alloprevotella in the colon. Conclusions Glycine supplementation is a nutritional strategy that may ameliorate C. rodentium ‐induced colitis by regulating ATF6α‐CHOP‐mediated ER stress and enhancing the abundance of Lactobacillus .